Biomedical Engineering and Bioengineering Commons^™

Interfacing Neural Models: Biocompatibility And Fabrication Of A Flexible, Self-Folding Microelectrode Array, Fernando A. Pesantez Torres

Electronic Theses & Dissertations (2024 - present)

Neurodegenerative diseases pose a formidable challenge in modern medicine, necessitating the development of advanced research tools that can elucidate their complex pathophysiology. Recent advancements in neurodegenerative disease research have led to the development of three-dimensional (3D) neurodegenerative organoids using human induced pluripotent stem cells (hiPSCs). These organoids closely mimic human brain architecture and functionality, providing a valuable tool for understanding complex diseases. Additionally, the ability to generate and study brain organoids consistently and in large quantities holds potential for a controlled in vitro setting and high-throughput drug screening. However, these models are complex systems requiring specialized maintenance, analysis, and manipulation …

Synthesis And Assessment Of Biobased Acrylated Epoxidized Soybean Oil Resins For Stereolithography 3d Printing Of Microfluidic Devices, Natalie S. Romero Figueroa

College of Graduate Studies: Theses & Dissertations

This research focuses on the development and characterization of a biobased photocurable resin synthesized from soybean oil for use in stereolithography (SLA) 3D printing of microfluidic devices. The study explores a sustainable alternative to petroleum-based resins by performing an acrylation reaction on epoxidized soybean oil (ESO) to produce acrylated epoxidized soybean oil (AESO), which was then formulated into a photocurable resin with the addition of a photo initiator. The fabrication process involved designing microfluidic molds in SolidWorks and printing them using an Elegoo Mars 4 SLA printer under various exposure and layer thickness parameters. The printed samples consisted of microchannels …

Enhancing The Mechanical Properties Of Sla 3d-Printed Bio-Resin From Linseed Oil Using Cellulose And Lignin Biopolymers, Chukwunonso A. Ikedionu

College of Graduate Studies: Theses & Dissertations

Abstract

This research explores the development of bio resin from linseed oil by the process of epoxidation and acrylation to produce acrylated epoxidized linseed oil (AELO). Lignin and cellulose biopolymers were added as reinforcement at varying weight fractions of 1 wt.%, 2.5 wt.%, and 5 wt.%, and their mechanical performance was compared against pure AELO. The formulations were printed using an Elegoo SLA 3D printer to create standardized test specimens like tensile bars, compression cylinders, and hardness blocks, which were all prepared according to the ASTM testing standard.

The results indicate that reinforcement effects depend on both filler type and …

Optimization Of Small-Scale Bioreactors For Increased Pdna Production And Yield, Laura M. Hills

Honors Theses and Capstones

No abstract provided.

Scalable Fabrication Of High-Payload Dendrimer-Based Nanoparticles For Targeted Atherosclerosis Therapy, Huari Kou, Lin Qi, Da Huang, Jiandong Wu, Honglan Shi, Hu Yang

Chemistry Faculty Research & Creative Works

Nanoparticle-based therapeutics hold promise for the treatment of atherosclerosis, but challenges such as low drug-loading capacity and a lack of scalable, controllable production hinder their clinical translation. Flash nanoprecipitation, a continuous synthesis method, offers a potential solution for scalable and reproducible nanoparticle production. In this study, we employed a custom-designed multi-inlet vortex mixer to perform cross-linking reaction-enabled flash nanoprecipitation, facilitating controlled and scalable synthesis of cross-linked Poly amidoamine (PAMAM) dendrimer nanoparticles. Notably, this approach allows simultaneous nanoparticle cross-linking and drug loading in a single step. The mannose moiety enabled specific targeting of macrophages via mannose receptors, enhancing the localization of …

Evaluation Of The Dnazyme Gr5 For The Determination Of Lead Speciation In Natural Waters, Gaganprit Gill

Theses and Dissertations (Comprehensive)

This thesis explores the development and application of a DNAzyme-based biosensor designed to detect labile metal species in environmental samples. Real time and on-site monitoring of labile metal fractions would make a valuable contribution to environmental management, as these fractions are the most bioavailable and pose significant toxicity risks to aquatic organisms. Conventional methods for detecting labile metals, while effective, are often burdened by high costs, complexity, and lengthy processing times, making them less ideal for rapid and widespread environmental assessments.

The first manuscript of this thesis (chapter 2) establishes the fundamental capabilities of the Pb²⁺-specific DNAzyme GR5 …

Targeting Myeloid Cell Iron Metabolism In Salmonella-Induced Colitis, Mariella Arcos Padilla

Biomedical Engineering ETDs

Salmonellosis is a severe infection caused by Salmonella enterica serovar Typhimurium, leading to significant global morbidity and mortality.

Previous studies have shown that mice lacking the iron storage protein ferritin heavy chain (FTH1) in myeloid cells exhibit worsened Salmonella infection. Nuclear receptor co-activator 4 (NCOA4) directs FTH1 autophagic degradation to release iron from storage during conditions of low iron. However, the role of myeloid NCOA4 in regulating bacterial infections remains unclear.

Here, we found that myeloid NCOA4 deficiency augments spleen iron levels and increases cellular iron accumulation, oxidative stress, and ferroptosis in bone marrow-derived macrophages (BMDM) cells. This deficiency also …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Phagolysosomes Break Down The Membrane Of A Non-Apoptotic Corpse Independent Of Macroautophagy, Shruti Kolli, Cassidy J. Kline, Kimya M. Rad, Ann M. Wehman

Biological Sciences: Faculty Scholarship

Cell corpses must be cleared in an efficient manner to maintain tissue homeostasis and regulate immune responses. Ubiquitin-like Atg8/LC3 family proteins promote the degradation of membranes and internal cargo during both macroautophagy and corpse clearance, raising the question how macroautophagy contributes to corpse clearance. Studying the clearance of non-apoptotic dying polar bodies in Caenorhabditis elegans embryos, we show that the LC3 ortholog LGG-2 is enriched inside the polar body phagolysosome independent of autophagosome formation. We demonstrate that ATG-16.1 and ATG-16.2, which promote membrane association of lipidated Atg8/LC3 proteins, redundantly promote polar body membrane breakdown in phagolysosomes independent of their role …

Noncontact Diffuse Reflectance Spectroscopy Of Synovial Fluid Samples For Rapid Identification Of Infections, Erin E. Drewke, Robert L. Brand, Caroline G. Geels, Hanna K. Jensen, Kevin Wong, Jarret D. Sanders, Narasimhan Rajaram

Biomedical Engineering Faculty Publications and Presentations

Severe joint infections, such as septic arthritis, require rapid diagnostic testing of the synovial fluid aspirated from joints level so that a surgical team can be assembled quickly. We present a diffuse reflectance spectroscopy (DRS) system for noncontact determination of infection. Using a light-tight syringe holder and fiber optic probe, diffusely reflected light from 475 to 655 nm was acquired from 18 patient samples through the wall of a syringe in a noncontact and sterile manner. We determined the reflectance ratios at two different wavelengths—R ₄₉₀/R ₆₀₀ and R ₅₈₀/R ₆₀₀ and found statistically significant …

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring

Biomedical Sciences Theses & Dissertations

The dynamic cellular microenvironment, made up of resident cells and various macromolecules, differs markedly across tissues in the body. The multidirectional signals that cells receive from this microenvironment, along with the signaling they send back, heavily influence their physiology and behavior. Recent important findings have further validated this notion as the mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) driving changes in metabolic reprogramming and cancer fate redirection is understudied. The work presented in this dissertation focuses on exploring the impact of …

Nanopore Signal Deviations From Pseudouridine Modifications In Rna Are Sequence-Specific: Quantification Requires Dedicated Synthetic Controls, Amr Makhamreh, Sepideh Tavakoli, Ali Fallahi, Xinqi Kang, Howard Gamper, Mohammad Nabizadehmashhadtoroghi, Miten Jain, Ya-Ming Hou, Sara H Rouhanifard, Meni Wanunu

Department of Biochemistry and Molecular Biology Faculty Papers

Chemical modifications to mRNA respond dynamically to environmental cues and are important modulators of gene expression. Nanopore direct RNA sequencing has been applied for assessing the presence of pseudouridine (ψ) modifications through basecalling errors and signal analysis. These approaches strongly depend on the sequence context around the modification, and the occupancies derived from these measurements are not quantitative. In this work, we combine direct RNA sequencing of synthetic RNAs bearing site-specific modifications and supervised machine learning models (ModQuant) to achieve near-analytical, site-specific ψ quantification. Our models demonstrate that the ionic current signal features important for accurate ψ classification are sequence …

Cellular Energy Cycle Mediates An Advection-Like Forward Cell Flow To Support Collective Invasion, Jian Zhang, Jenna Mosier, Yusheng Wu, Logan Waddle, Paul V. Taufelele, Wenjun Wang, Heng Sun, Cynthia A. Reinhart-King

Biomedical Engineering Faculty Publications and Presentations

Collective cell migration is a model for nonequilibrium biological dynamics, which is important for morphogenesis, pattern formation, and cancer metastasis. The current understanding of cellular collective dynamics is based primarily on cells moving within a 2D epithelial monolayer. However, solid tumors often invade surrounding tissues in the form of a stream-like 3D structure, and how biophysical cues are integrated at the cellular level to give rise to this collective streaming remains unclear. Here, it is shown that cell cycle-mediated bioenergetics drive a forward advective flow of cells and energy to the front to support 3D collective invasion. The cell division …

Single-Molecule Orientation Imaging Reveals The Nano-Architecture Of Amyloid Fibrils Undergoing Growth And Decay, Brian Sun, Tianben Ding, Weiyan Zhou, Tara S. Porter, Matthew D. Lew

Electrical & Systems Engineering Publications and Presentations

Amyloid-beta (Aβ42) aggregates are characteristic Alzheimer’s disease signatures, but probing how their nanoscale architectures influence their growth and decay remains challenging using current technologies. Here, we apply time-lapse single-molecule orientation-localization microscopy (SMOLM) to measure the orientations and rotational “wobble” of Nile blue (NB) molecules transiently binding to Aβ42 fibrils. We correlate fibril architectures measured by SMOLM with their growth and decay over the course of 5 to 20 min visualized by single-molecule localization microscopy (SMLM). We discover that stable Aβ42 fibrils tend to be well-ordered and signified by well-aligned NB orientations and small wobble. SMOLM also shows that increasing order …

Evaluation Of The Efficiency Of Muscle-Specific Promoters To Express Non-Endogenous Proteins In Skeletal Muscle, Gabrielle Bulliard, Made Harumi Padmaswari, Christopher E. Nelson

Biomedical Engineering Undergraduate Honors Theses

Gene therapies are emerging as powerful tools for treating genetic diseases and cancers, offering the potential for a permanent cure. Hemophilia B, affecting approximately 6,000 men in the U.S., results from a deficiency in coagulation factor IX protein (FIX), which is crucial for blood clotting. A substantial portion of patients, over 40%, suffer from severe hemophilia B, experiencing spontaneous, prolonged bleeding. Current prophylactic treatments involve frequent coagulation factor infusions, yet a curative approach would alleviate this burden. Gene editing technologies like CRISPR-Cas systems show promise for correcting genetic mutations, but the diverse nature of factor IX gene (F9) …

Testing Resilience Of Microalgae Biofilms When Exposed To Hydrothermal Liquefaction Aqueous Phase, Davis Riley Haag

Undergraduate Honors Capstone Projects

There are a multitude of experimental and processing techniques in the bioenergy field that produce sustainable and carbon negative to carbon neutral methods of converting renewable resources into biologically based hydrocarbons. One example of a process is hydrothermal liquefaction (HTL) which specializes in converting wet biomass into biocrude oil. One reason that these processes are not used outside experimental testing is due to the high cost of performing these processes. There is potential to move these processes to larger scale testing and eventually industrial adaptation if breakthroughs are made to offset the process expenses. There is a waste product produced …

Spontaneous Alignment Of Myotubes Through Myogenic Progenitor Cell Migration, Lauren E. Mehanna, Adrianna R. Osborne, Charlotte A. Peterson, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

In large-volume muscle injuries, widespread damage to muscle fibers and the surrounding connective tissue prevents myogenic progenitor cells (MPCs) from initiating repair. There is a clinical need to rapidly fabricate large muscle tissue constructs for integration at the site of large volume muscle injuries. Most strategies for myotube alignment require microfabricated structures or prolonged orientation times. We utilize the MPC’s natural propensity to close gaps across an injury site to guide alignment on collagen I. When MPCs are exposed to an open boundary free of cells, they migrate unidirectionally into the cell-free region and align perpendicular to the original boundary …

Rational Design Of Peptide-Based Materials Informed By Multiscale Molecular Dynamics Simulations, Dhwanit Rahul Dave

Dissertations, Theses, and Capstone Projects

The challenge of establishing a sustainable and circular economy for materials in medicine and technology necessitates bioinspired design. Nature's intricate machinery, forged through evolution, relies on a finite set of biomolecular building blocks with through-bond and through-space interactions. Repurposing these molecular building blocks requires a seamless integration of computational modeling, design, and experimental validation. The tools and concepts developed in this thesis pioneer new directions in peptide-materials design, grounded in fundamental principles of physical chemistry. We present a synergistic approach that integrates experimental designs and computational methods, specifically molecular dynamics simulations, to gain in-depth molecular insights crucial for advancing the …

Advancing Biological Applications Through Microfluidic-Based Tool Development, K.M. Taufiqur Rahman

Electronic Theses and Dissertations

This research undertook an interdisciplinary approach, integrating bioengineering, microbiology, molecular biology, and systems biology to investigate bacterial dynamics behavior. Specifically, it delved into the development of microfluidic devices for biological applications such as bacterial cell counts, real-time observation of plant roots (here, specialized lectin-coated microbeads are used that mimic root characteristics), and soil microbe interactions. Furthermore, Next-Generation Sequencing and systems biology methodologies were employed to explore the intricate, multifaceted survival mechanisms of Escherichia coli persister population. Studying and quantifying persisters or testing for the existence of VBNC (viable but nonculturable) is challenging. These experiments require precise counts. It has been …

Transparent And Conductive Gallium Oxide Electrode For Simultaneous Recording And Optogenetic Stimulation, Christopher Patrick Carey

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neural electrode technology has been around for centuries since the times of Galvani. In early electrophysiology experiments metal wires were used to induce contractions in dissected animals. The metal wire electrode has since been a standard tool to both stimulate and record neural activity. In the past two decades, a new strategy for neural stimulation has been formulated based on the emergent field of optogenetics. Optogenetics refers to the use of light-sensitive proteins genetically imbedded in the membrane of a neuron to elicit neural activity. This technique offers more selectivity in the stimulation of neurons. Typical optogenetic neural electrodes, or …

Dna I-Motifs: Biophysical Characterization And Structure-Property Correlation As Foundation For Functional Material Design, Alexander Minasyan

Graduate Research Theses & Dissertations

Over the past decades, nucleic acids have emerged as crucial frameworks with significance in biological systems and functional material engineering. Cytosine-rich deoxyribonucleotide sequences can form quadruplex structures a.k.a. i-motifs. Recently, i-motifs have attracted scientific interest in biological and material design areas.

In this work, we systematically investigate an effect of structured and unstructured modifications such as hairpins, stems, loops and overhangs on the kinetic and thermodynamic properties of DNA i-motifs. We demonstrate that the modifications can influence i-motif’s stability and folding/unfolding rates: thus, double stranded stems and hairpins are the best at stabilizing i-motifs and increasing kinetic rates of folding. …

Method For Continuous Fabrication Of Multi-Functional Nanogels, Hu Yang, Da Huang

Patents

Nanogels and methods of synthesizing and using these nanogels are provided. The nanogels are formed by mixing a building block (e.g., polymer), crosslinker, preferably a target (e.g., biomedical compound or molecule), and a solvent in a multi-inlet vortex mixer, so as to cause the polymer and crosslinker to react and form a chemically crosslinked polymer network. In embodiments including a target, the target will be interspersed in and among that network and can be physically embedded and/or chemically bound therein.

Reducing Food Scarcity: The Benefits Of Urban Farming, S.A. Claudell, Emilio Mejia

Journal of Nonprofit Innovation

Urban farming can enhance the lives of communities and help reduce food scarcity. This paper presents a conceptual prototype of an efficient urban farming community that can be scaled for a single apartment building or an entire community across all global geoeconomics regions, including densely populated cities and rural, developing towns and communities. When deployed in coordination with smart crop choices, local farm support, and efficient transportation then the result isn’t just sustainability, but also increasing fresh produce accessibility, optimizing nutritional value, eliminating the use of ‘forever chemicals’, reducing transportation costs, and fostering global environmental benefits.

Imagine Doris, who is …

Air-Jet Bioprinting Of Stem Cell-Encapsulated Alginate Micro-Droplets For Organoid Biomanufacturing, Mirabella B. Stump

Electronic Theses and Dissertations

Biomanufactured 3D-organoids show promise for modeling and treating various conditions, particularly insulin-dependent diabetes mellitus (type-1 diabetes). Pancreatic islet organoids serve as sustainable sources of insulin-producing β-cells, potentially restoring insulin regulation in patients and providing a long-term solution for diabetes. Hydrogel droplet printing is an emerging technique in regenerative medicine due to its advantageous tunability and biocompatibility; however, challenges of consistency, quality control, and scalability persist. To address these issues, we developed a novel air-jetting based droplet bioprinting system for the generation of monodispersed alginate micro-droplets. The objective of this project was to incorporate human induced pluripotent stem cells (hiPSCs) into …

Structural Characterization Of Cardiomyocyte Microenvironment In Murine Myocardium By Multimodal Stimulated Emission Depletion Microscopy, Zhao Zhang

All Dissertations

Cardiomyopathy, a disease of the heart muscle, is characterized by structural and functional abnormalities of the myocardium, in the absence of coronary artery disease, hypertension, valvular disease or congenital heart disease. In 2020, there were approximately 6.11 million prevalent cases of cardiomyopathy and myocarditis, and 0.37 million related deaths worldwide. Many affected individuals are asymptomatic, and chronically treated patients are at risk of heart failure. Within the myocardium, cardiomyocytes reside in a complex and dynamic extracellular matrix (ECM), consisting of basement membrane and interstitial matrix. The interactions between cardiomyocytes and myocardial ECM play a critical role in maintaining cardiac geometry …

Evolutionary Conservation And Times Of Action Of Heterochronic Genes, Maria Ivanova

Theses and Dissertations

The heterochronic pathway of C. elegans is the most well-characterized system to date for controlling the sequence and timing of developmental events. However, we still have critical unanswered questions to address. First, little is known about the evolution of the heterochronic pathway, and of developmental timing in general. To determine if the roles of major heterochronic genes are conserved, I made mutants in orthologs of these genes in C. briggsae, using CRISPR/Cas9. My studies revealed a significant drift in the roles of some of the genes, although all of them are still involved in the developmental timing regulation, and several …

Pulsed Electric Field Ablation: Mechanisms Of Differential Cell Sensitivity And Methods To Mitigate Neuromuscular Excitation, Emily Gudvangen

Biomedical Engineering Theses & Dissertations

Ablation therapies aim to destroy tumors while maintaining minimal damage to surrounding healthy tissue. Pulsed electric field (PEF) ablation targets the cell membrane during the destruction of tissues, which consequently spares extracellular structures such as ducts and blood vessels, leaving the framework for tissue regeneration. However, the utility of PEF is limited by neuromuscular excitation, causing pain and involuntary muscle contraction. To identify PEF protocols that efficiently ablate tissue while minimizing neuromuscular stimulation, various PEF protocols differing in pulse duration, shape, and repetition rate were tested. The ratio of cell death and nerve excitation thresholds, which determines the range of …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Nanoscale Modeling Of Membrane Systems Under Mechanical Deformation In Traumatic Brain Injury Using Molecular Dynamics, Anh Thi Ngoc Vo

Theses and Dissertations

Neuronal membrane disruption and mechanoporation are nanoscale damage mechanisms that critically affect brain cell viability during traumatic brain injury (TBI). These nanoscale cellular impairments are elusive in experiments and necessitate in silico approaches such as molecular dynamics (MD) simulations. Implementing MD, this research aims to investigate the effects of different key factors related to membrane deformation and damage, including force field resolutions, lipid compositions, and loading conditions.

To examine the impact of force field resolution, MD deformation simulations were conducted on 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) lipid bilayer membranes, using all-atom (AA), united-atom (UA), and coarse-grained Martini (CG-M) force fields. The mechanical responses …

Methods To Study Activity Dependent Protein Synthesis In Autism Spectrum Disorder, Megan Webb, Karin F K Ejendal, Tamara L. Kinzer-Ursem

Discovery Undergraduate Interdisciplinary Research Internship

It is estimated by the World Health Organization that 1 in 100 children have autism spectrum disorder (ASD), a condition characterized by neurological differences that may impact a person’s learning or behavior. Clinically, ASD symptoms are alleviated with behavioral or pharmacological therapies, however, not all patients respond to these interventions. Deep brain stimulation (DBS) is a promising treatment of Parkinson’s disease that could also be effective in treating ASD. SynGAP1 is a protein involved in neuronal action that is crucial for regulating synaptic plasticity. Mutations in the SYNGAP1 gene causing haploinsufficiency can result in the manifestation of ASD symptoms. This …